Suboptimal responses in chronic myeloid leukemia: Milestones and mechanisms

Expert Review of Hematology

Volumn 2, Issue 1, 2009, Pages 81-91

  Porkka, Kimmo ^a   Mustjoki, Satu ^a   Simonsson, Bengt ^b  

^a UNIVERSITY OF HELSINKI   (Finland)

^b UPPSALA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Chronic myeloid leukemia; Drug resistance; Guidelines; Imatinib

Indexed keywords

BCR ABL PROTEIN; BREAST CANCER RESISTANCE PROTEIN; DASATINIB; GLYCOPROTEIN P; IMATINIB; MULTIDRUG RESISTANCE PROTEIN 1; NILOTINIB; OCTAMER TRANSCRIPTION FACTOR 1;

BCR ABL GENE; CANCER RELAPSE; CANCER SURVIVAL; CARCINOGENESIS; CHRONIC MYELOID LEUKEMIA; CYTOPENIA; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG MECHANISM; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; FLUID RETENTION; GASTROINTESTINAL DISEASE; GENE AMPLIFICATION; GENE MUTATION; GENE OVEREXPRESSION; HUMAN; IMMUNOGENICITY; MUSCULOSKELETAL PAIN; ONCOGENE; OVERALL SURVIVAL; PATIENT COMPLIANCE; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROGNOSIS; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; REVIEW; SIDE EFFECT; STEM CELL TRANSPLANTATION; TREATMENT RESPONSE;

ANTINEOPLASTIC AGENTS; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; PIPERAZINES; PROGNOSIS; PYRIMIDINES; TREATMENT OUTCOME;

EID: 77953428513     PISSN: 17474086     EISSN: None     Source Type: Journal    
DOI: 10.1586/17474086.2.1.81     Document Type: Review

References (85)

1. Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood 96, 3343-3356 (2000).
2. Kantarjian HM, Talpaz M, Giles F, O'Brien S, Cortes J. New insights into the pathophysiology of chronic myeloid leukemia and imatinib resistance. Ann. Intern. Med. 145, 913-923 (2006). (Pubitemid 351639967)
3. Cortes J. Natural history and staging of chronic myelogenous leukemia. Hematol. Oncol. Clin. North Am. 18, 569-584 (2004). (Pubitemid 38969132)
4. Sawyers CL, Hochhaus A, Feldman E et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a Phase II study. Blood 99, 3530-3539 (2002). (Pubitemid 34534519)
5. Wadhwa J, Szydlo RM, Apperley JF et al. Factors affecting duration of survival after onset of blastic transformation of chronic myeloid leukemia. Blood 99, 2304-2309 (2002).
6. Druker BJ, Tamura S, Buchdunger E et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. 2, 561-566 (1996).
7. Gambacorti-Passerini C, le Coutre P, Mologni L et al. Inhibition of the ABL kinase activity blocks the proliferation of Bcr/Abl+ leukemic cells and induces apoptosis. Blood Cells Mol. Dis. 23, 380-394 (1997).
8. Druker BJ, Guilhot F, O'Brien SG et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N. Engl. J. Med. 355, 2408-2417 (2006).
9. Brave M, Goodman V, Kaminskas E et al. Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin. Cancer Res. 14, 352-359 (2008).
10. Hazarika M, Jiang X, Liu Q et al. Tasigna for chronic and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukemia resistant to or intolerant of imatinib. Clin. Cancer Res. 14, 5325-5331 (2008).
11. de Lavallade H, Apperley JF, Khorashad JS et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-totreat analysis. J. Clin. Oncol. 26, 3358-3363 (2008).
12. Marin D, Milojkovic D, Olavarria E et al. European LeukemiaNet criteria for failure or sub-optimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood 112(12), 4437-4444 (2008).
13. Alvarado Y, Kantarjian H, Faderl S et al. Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in long-term outcome for patients with chronic phase chronic myeloid leukemia. ASH Annual Meeting Abstracts. Blood 110, 573a (2007) (Abstract 1932).
14. Kantarjian HM, Cortes J, Guilhot F, Hochhaus A, Baccarani M, Lokey L. Diagnosis and management of chronic myeloid leukemia: a survey of American and European practice patterns. Cancer 109, 1365-1375 (2007).
15. Baccarani M, Saglio G, Goldman J et al. Evolving concepts in the management of chronic myeloid leukemia. Recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 108, 1809-1820 (2006).
16. Hughes T, Deininger M, Hochhaus A et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 108, 28-37 (2006).
17. Hochhaus A, Dreyling M. Chronic myelogenous leukemia: ESMO clinical recommendations for the diagnosis, treatment and follow-up. Ann. Oncol. 19(Suppl. 2), ii63-ii64 (2008).
18. Australasian Leukemia and Lymphoma Group (ALLG) Myeloproliferative Disease Subcommittee. Australasian treatment guidelines for de novo CML CP, v1.0. Canterbury Health Laboratories, Christchurch, New Zealand (2006).
19. Laneuville P, Barnett MJ, Bélanger R et al. Recommendations of the Canadian Consensus Group on the management of chronic myeloid leukemia. Curr. Oncol. 13, 201-221 (2006).
20. Hughes TP, Kaeda J, Branford S et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N. Engl. J. Med. 349, 1423-1432 (2003).
21. Kantarjian H, Sawyers C, Hochhaus A et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N. Engl. J. Med. 346, 645-652 (2002).
22. Lahaye T, Riehm B, Berger U et al. Response and resistance in 300 patients with BCR-ABL-positive leukemias treated with imatinib in a single center: a 4.5-year follow-up. Cancer 103, 1659-1669 (2005).
23. Quintas-Cardama A, Kantarjian HM, Jones D et al. Delayed achievement of molecular responses is associated with increased risk of progression among patients with chronic myelogenous leukemia in chronic phase treated with imatinib. ASH Annual Meeting Abstracts. Blood 108, A613 (2006) (Abstract 432).
24. Kantarjian H, O'Brien S, Shan J et al. Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia: need for new response definitions? Cancer 112, 837-845 (2008).
25. Tam CS, Kantarjian H, Garcia-Manero G et al. Failure to achieve a major cytogenetic response by 12 months defines inadequate response in patients receiving nilotinib or dasatinib as second or subsequent line therapy for chronic myeloid leukemia. Blood 112, 516-518 (2008).
26. Branford S, Rudzki Z, Harper A et al. Imatinib produces significantly superior molecular responses compared to interferon a plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Leukemia 17, 2401-2409 (2003).
27. Hughes T , Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukaemia. Blood Rev. 20, 29-41 (2006).
28. Cortes J, Talpaz M, O'Brien S et al. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin. Cancer Res. 11, 3425-3432 (2005). (Pubitemid 40627896)
29. Wang L, Pearson K, Ferguson JE, Clark RE. The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia. Br. J. Haematol. 120, 990-999 (2003).
30. Press RD, Love Z, Tronnes AA et al. BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML. Blood 107, 4250-4256 (2006).
31. Merx K, Muller MC, Kreil S et al. Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon a. Leukemia 16, 1579-1583 (2002).
32. Iacobucci I, Saglio G, Rosti G et al. Achieving a major molecular response at the time of a complete cytogenetic response (CCgR) predicts a better duration of CCgR in imatinib-treated chronic myeloid leukemia patients. Clin. Cancer Res. 12, 3037-3042 (2006).
33. Paschka P, Muller MC, Merx K et al. Molecular monitoring of response to imatinib (Glivec) in CML patients pretreated with interferon a. Low levels of residual disease are associated with continuous remission. Leukemia 17, 1687-1694 (2003).
34. Branford S, Rudzki Z, Parkinson I et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations. Blood 104, 2926-2932 (2004).
35. Wang L, Knight K, Lucas C, Clark RE. The role of serial BCR-ABL transcript monitoring in predicting the emergence of BCR-ABL kinase mutations in imatinib-treated patients with chronic myeloid leukemia. Haematologica 91, 235-239 (2006).
36. Press RD, Galderisi C, Yang R et al. A half-log increase in BCR-ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response. Clin. Cancer Res. 13, 6136-6143 (2007).
37. Martinelli G, Soverini S, Rosti G, Cilloni D, Baccarani M. New tyrosine kinase inhibitors in chronic myeloid leukemia. Haematologica 90, 534-541 (2005). (Pubitemid 40592897)
38. Branford S. Chronic myeloid leukemia: molecular monitoring in clinical practice. Hematol. Am. Soc. Hematol. Educ. Program 2007, 376-383 (2007).
39. Branford S, Rudzki Z, Walsh S et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 102, 276-283 (2003).
40. Nicolini FE, Corm S, Le QH et al. Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(varphi)-LMC GROUP). Leukemia 20, 1061-1066 (2006).
41. Soverini S, Martinelli G, Rosti G et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J. Clin. Oncol. 23, 4100-4109 (2005).
42. Soverini S, Gnani A, Colarossi S et al. ABL kinase domain mutations are infrequent in early-chronic phase chronic myeloid leukemia patients resistant to imatinib. Haematologica 93(Suppl. 1), 43 (2008) (Abstract 0107).
43. Soverini S, Colarossi S, Gnani A et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin. Cancer Res. 12, 7374-7379 (2006).
44. Hochhaus A, Kreil S, Corbin AS et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 16, 2190-2196 (2002).
45. Gorre ME, Mohammed M, Ellwood K et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293, 876-880 (2001).
46. Barnes DJ, Palaiologou D, Panousopoulou E et al. Bcr-Abl expression levels determine the rate of development of resistance to imatinib mesylate in chronic myeloid leukemia. Cancer Res. 65, 8912-8919 (2005).
47. Mohamed AN, Pemberton P, Zonder J, Schiffer CA. The effect of imatinib mesylate on patients with Philadelphia chromosomepositive chronic myeloid leukemia with secondary chromosomal aberrations. Clin. Cancer Res. 9, 1333-1337 (2003).
48. Marktel S, Marin D, Foot N et al. Chronic myeloid leukemia in chronic phase responding to imatinib: the occurrence of additional cytogenetic abnormalities predicts disease progression. Haematologica 88, 260-267 (2003).
49. Cortes JE, Talpaz M, Giles F et al. Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. Blood 101, 3794-3800 (2003). (Pubitemid 36857848)
50. Schoch C, Haferlach T, Kern W et al. Occurrence of additional chromosome aberrations in chronic myeloid leukemia patients treated with imatinib mesylate. Leukemia 17, 461-463 (2003).
51. O'Dwyer ME, Mauro MJ, Blasdel C et al. Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Blood 103, 451-455 (2004).
52. Donato NJ, Wu JY, Stapley J et al. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 101, 690-698 (2003).
53. Wu J, Meng F, Kong LY et al. Association between imatinib-resistant BCR-ABL mutation-negative leukemia and persistent activation of LYN kinase. J. Natl Cancer Inst. 100, 926-939 (2008).
54. Dai Y, Rahmani M, Corey SJ, Dent P, Grant S. A Bcr/Abl-independent, Lyn-dependent form of imatinib mesylate (STI-571) resistance is associated with altered expression of Bcl-2. J. Biol. Chem. 279, 34227-34239 (2004).
55. Cortes J, Kantarjian H. New targeted approaches in chronic myeloid leukemia. J. Clin. Oncol. 23, 6316-6324 (2005).
56. Mohty M, Blaise D, Olive D, Gaugler B. Imatinib: the narrow line between immune tolerance and activation. Trends Mol. Med. 11, 397-402 (2005).
57. Mustjoki S, Lundan T, Knuutila S, Porkka K. Appearance of bone marrow lymphocytosis predicts an optimal response to imatinib therapy in patients with chronic myeloid leukemia. Leukemia 21, 2363-2368 (2007).
58. Chen CI, Maecker HT, Lee PP, Development and dynamics of robust T-cell responses to CML under imatinib treatment. Blood 111, 5342-5349 (2008).
59. Sokal JE, Cox EB, Baccarani M et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood 63, 789-799 (1984).
60. White D, Saunders V, Lyons AB et al. In vitro sensitivity to imatinib-induced inhibition of ABL kinase activity is predictive of molecular response in patients with de novo CML. Blood 106, 2520-2526 (2005).
61. White D, Saunders V, Grigg A et al. Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia. J. Clin. Oncol. 25, 4445-4451 (2007).
62. Thomas J, Wang L, Clark RE, Pirmohamed M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood 104, 3739-3745 (2004).
63. White DL, Saunders VA, Dang P et al. OCT-1 mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107); reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood 108, 697-704 (2006).
64. Crossman LC, Druker BJ, Deininger MW, Pirmohamed M, Wang L, Clark RE. hOCT 1 and resistance to imatinib. Blood 106, 1133-1134 (2005).
65. Wang L, Giannoudis A, Lane S, Williamson P, Pirmohamed M, Clark RE. Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia. Clin. Pharmacol. Ther. 83, 258-264 (2008).
66. White DL, Saunders VA, Dang P et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood 110, 4064-4072 (2007).
67. Illmer T, Schaich M, Platzbecker U et al. P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia 18, 401-408 (2004).
68. Burger H, van Tol H, Brok M et al. Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol. Ther. 4, 747-752 (2005).
69. Picard S, Titier K, Etienne G et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood 109, 3496-3499 (2007).
70. Larson RA, Druker BJ, Guilhot F et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood 111, 4022-4028 (2008).
71. Gambacorti-Passerini C, Barni R, le Coutre P et al. Role of a1 acid glycoprotein in the in vivo resistance of human BCR-ABL+ leukemic cells to the Abl inhibitor STI571. J. Natl Cancer Inst. 92, 1641-1650 (2000).
72. Larghero J, Leguay T, Mourah S et al. Relationship between elevated levels of the a 1 acid glycoprotein in chronic myelogenous leukemia in blast crisis and pharmacological resistance to imatinib (Gleevec) in vitro and in vivo. Biochem. Pharmacol. 66, 1907-1913 (2003).
73. le Coutre P, Kreuzer KA, Na IK et al. Imatinib in Philadelphia chromosomepositive chronic phase CML patients: molecular and cytogenetic response rates and prediction of clinical outcome. Am. J. Hematol. 73, 249-255 (2003).
74. Tipping AJ, Deininger MW, Goldman JM, Melo JV. Comparative gene expression profile of chronic myeloid leukemia cells innately resistant to imatinib mesylate. Exp. Hematol. 31, 1073-1080 (2003).
75. McLean LA, Gathmann I, Capdeville R, Polymeropoulos MH, Dressman M. Pharmacogenomic analysis of cytogenetic response in chronic myeloid leukemia patients treated with imatinib. Clin. Cancer Res. 10, 155-165 (2004).
76. Hochhaus A, Druker B, Sawyers C et al. Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-a treatment. Blood 111, 1039-1043 (2008).
77. Jabbour E, Kantarjian H, Atallah E et al. Impact of imatinib mesylate dose escalation on resistance and sub-optimal responses to standard-dose therapy in patients with chronic myeloid leukemia. ASH Annual Meeting Abstracts. Blood 110, A313-A314 (2007) (Abstract 1035).
78. Rea D, Etienne G, Corm S et al. Imatinib mesylate dose escalation improves disease response in chronic-phase chronic myeloid leukaemia patients after cytogenetic or molecular suboptimal responses to standard doses of imatinib. ASH Annual Meeting Abstracts. Blood 110, A318a-A319 (2007) (Abstract 1052).
79. Kim DY, Kim HJ, Jeong JS et al. Efficacy of imatinib mesylate dose-escalation in CML patients showing suboptimal response to standard dose. ASH Annual Meeting Abstracts. Blood 110, A871 (2007) (Abstract 2967).
80. Hughes TP, Branford S, White DL et al. Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy. Blood 112, 3965-3973 (2008).
81. O'Hare T, Walters DK, Stoffregen EP et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 65, 4500-4505 (2005).
82. Weisberg E, Manley PW, Breitenstein W et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 7, 129-141 (2005).
83. Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat. Rev. Cancer 7, 345-356 (2007).
84. Shah NP, Kantarjian HM, Kim DW et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J. Clin. Oncol. 26, 3204-3212 (2008).
85. Kantarjian H, Pasquini R, Hamerschlak N et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized Phase 2 trial. Blood 109, 5143-5150 (2007). (Pubitemid 46890528)